Most bacterial pathogenesis studies have focused on mono-culture infections; however, it is clear that many bacterial infections are not simply the result of colonization with a single species, but rather ensue from the action of polymicrobial communities. Microbes within polymicrobial infections often display synergistic interactions that result in enhanced colonization, persistence and antibiotic resistance in the infection site. Such interactions have been particularly noted in polymicrobial soft tissue infections, such as those in burns and chronic wounds, although the molecular processes controlling these synergistic interactions are generally not known. Studies elucidating the genetic pathways involved in polymicrobial interactions that contribute to enhanced persistence in vivo is critical for a comprehensive understanding of synergy, and a necessary first step towards developing therapeutics to treat multi-species infections. The overall goal of this research plan is to examine, from a genomic standpoint, how interactions between opportunistic pathogens impact in vivo persistence in acute and chronic wound infections. To accomplish this goal, high-throughput genomics techniques will be employed to identify microbial genes that are required for and expressed during polymicrobial synergy.